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Levels of procoagulant microparticles expressing phosphatidylserine contribute to bleeding phenotype in patients with inherited thrombocytopenia
- Source :
- Blood Coagulation & Fibrinolysis. 32:480-490
- Publication Year :
- 2021
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2021.
-
Abstract
- Inherited thrombocytopenia is a heterogeneous group of hereditary disorders with varying bleeding tendencies, not simply related to platelet count. Platelets transform into different subpopulations upon stimulation, including procoagulant platelets and platelet microparticles (PMPs), which are considered critical for haemostasis. We aimed to investigate whether abnormalities in PMP and procoagulant platelet function were associated with the bleeding phenotype of inherited thrombocytopenia patients. We enrolled 53 inherited thrombocytopenia patients. High-throughput sequencing of 36 inherited thrombocytopenia related genes was performed in all patients and enabled a molecular diagnosis in 57%. Bleeding phenotype was evaluated using the ISTH bleeding assessment tool, dividing patients into bleeding (n = 27) vs. nonbleeding (n = 26). Unstimulated and ADP, TRAP or collagen-stimulated PMP and procoagulant platelet functions were analysed by flow cytometry using antibodies against granulophysin (CD63), P-selectin (CD62P), activated GPIIb/IIIa (PAC-1) and a marker for phosphatidylserine expression (lactadherin). Procoagulant platelets were measured in response to collagen stimulation. An in-house healthy reference level was available. Overall, higher levels of activated platelets, PMPs and procoagulant platelets were found in nonbleeding patients compared with the reference level. Nonbleeding patients had higher proportions of phosphatidylserine and PMPs compared with bleeding patients and the reference level, in response to different stimulations. Interestingly, this finding of high proportions of phosphatidylserine and PMPs was limited to PMPs, and not present in procoagulant platelets or platelets. Our findings indicate that nonbleeding inherited thrombocytopenia patients have compensatory mechanisms for improved platelet subpopulation activation and function, and that generation of phosphatidylserine expressing PMPs could be a factor determining bleeding phenotype in inherited thrombocytopenia.
- Subjects :
- Adult
Blood Platelets
Male
Hemorrhage
Phosphatidylserines
Flow cytometry
Young Adult
chemistry.chemical_compound
Cell-Derived Microparticles
medicine
Humans
Platelet
Platelet activation
Blood Coagulation
Aged
Lactadherin
medicine.diagnostic_test
CD63
biology
business.industry
Hematology
General Medicine
Phosphatidylserine
Middle Aged
Platelet Activation
Thrombocytopenia
Phenotype
chemistry
Immunology
biology.protein
Female
Antibody
business
Subjects
Details
- ISSN :
- 14735733 and 09575235
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- Blood Coagulation & Fibrinolysis
- Accession number :
- edsair.doi.dedup.....4b2ecbc0e0faad62627a8bc26b83cef1